PROJECT SUMMARY The main objective of the Animal and Cell Model (ACM) Core is to provide animal and innovative cell culture models to the Project investigators and to coordinate and standardize the shared use of the models. Integrated into the ACM Core is the Pathology Sub-Core, which will process animal tissues to meet the needs for the individual projects. The impact of obesity on PDAC will be investigated in KC mice with diet-induced obesity (DIO) or genetically-induced obesity, which will allow to distinguish direct tumor promoting effects of dietary components from true obesity effects. For the DIO model, animals will be randomly allocated to either a control diet or a high fat, high calorie diet (HFCD) and the effect on tumor development assessed. For the genetically- induced obesity model, KC mice will be crossed into the leptin deficient ob/ob background (KCO). The ACM Core will carry out in collaboration with all three projects the main interventional study, in which KC mice are treated with statins. Tissues from this large study will be shared among and analyzed by all three projects. In addition to the main animal study, the ACM Core will conduct Project-specific interventions and will back-cross the KC model into additional genetic backgrounds. The main objectives of the Core are 1) to provide animal- related services and novel cell culture models to all Projects, 2) to minimize duplication of effort and reduce costs by coordinating experiments (shared animal and tissue use), and 3) to reduce variability introduced by different environments and husbandry and to ensure consistency in animal handling and data collection (concentration of resources and expertise). Services that the ACM Core provides for each Project include: obtaining and maintaining institutional approval, designing the animal studies in terms of logistics and statistical power calculations (together with Project PI's and Biostatistics Sub-Core), maintaining animal strains and setting up breeding pairs, genotyping of all animals, randomization of animals to experimental groups, preparation and administration of experimental diets or interventions, daily monitoring and animal care, euthanasia of animals, harvest of tissues and blood at sacrifice, processing tissue, e.g. fixing in formalin and embedding in paraffin, and sectioning (together with the Pathology Sub-Core), histopathological evaluation of tissue sections (together with the Pathology Sub-Core), generation of primary cell cultures (PanINs and murine pancreatic cancer), generating the murine and human pancreatic organoid cultures, storage of raw data, central banking of tissues and biological samples, distribution of tissues to individual Projects, discussion of results with Project Leaders, and training of Project investigators in animal procedures (if desired).